01. Universidade Federal Rural de Pernambuco - UFRPE (Sede)
URI permanente desta comunidadehttps://arandu.ufrpe.br/handle/123456789/1
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Item Síntese de 1H-1,2,3-triazol glicopiranosídeos análogos de nucleosídeos com potencial atividade antiviral(2021-12-09) Silva, Carla Jasmine Oliveira e; Oliveira, Ronaldo Nascimento de; http://lattes.cnpq.br/9071551767043294; http://lattes.cnpq.br/6278050350925332In this work, new nucleoside analogues containing the heterocyclics 1,2,3-triazol and pyrimidine conjugated with glycopyranosides were synthesized. Initially, the construction of our first synthetic block was carried out: the [beta]-azido-glycosides 3a-c, from three subsequent steps. The acetylation reaction of the carbohydrates D-(+)-Glucose, D-(+)-Galactose and L-(+)-Arabinose provided the O-acetyl-glycosides 1a-c, which were used in the next step with a solution 33 % HBr/AcOH to obtain [alfa]-bromo-glycosides 2a-c. Finally, we continued with the azidation reaction that formed the [beta]-azido-glycosides with moderate yields of 49% (3a) and 55% (3b) after crystallization in dichloromethane/ethanol (1:1); and 55% (3b) and 45% (3c) after purification by column chromatography (hexane/ethyl acetate, 8:2). The second synthetic block was prepared from the reaction of the nucleotidic bases, uracil and fluorouracil, with the propargyl bromide which provided the N1-,N3-bis-alkylated pyrimidine bases 4a-b with yields of 88% and 96%. Thus, the triazole nuclei were obtained through the copper-catalyzed 1,3-dipolar cycloaddition reaction between [beta]-azido-glycosides 3a-c and N1-,N3-bis-alkylated pyrimidine bases 4a-c. The disubstituted 1,2,3-triazole derivatives 5a-i were synthesized in excellent yields between 82-99%, and with the reaction time reduced to 1 hour compared to the literature, using 20 mol% of Cu(I) and 20 mol% Et3N.Item Estudo in vitro de avaliação da eficácia de novos compostos derivados de triazol frente a cepas sensíveis de Mycobacterium tuberculosis(2021-07-15) Rodrigues, Danielle Martiniano da Silva; Porto, Ana Lúcia Figueiredo; Pimentel, Lílian Maria Lapa Montenegro; http://lattes.cnpq.br/6066865382706623; http://lattes.cnpq.br/4989617783837981; http://lattes.cnpq.br/3260001484566380Tuberculosis is an infectious disease responsible for a high number of cases worldwide. Caused by the Mycobacterium tuberculosis species, it is transmitted from person to person through the airway, through the inhalation of bacilli from an infected individual, with positive bacilloscopy. Conventional treatment consists of the use of four first-line drugs: rifampicin, ethambutol, isoniazid and pyrazinamide. As a result of low therapeutic adherence, the world is currently facing a major problem of bacterial resistance, which makes treatment difficult, making it more toxic and longer, and may last for up to two years. For this reason, it is necessary to develop new molecules capable of eliminating the bacillus that causes tuberculosis quickly and with little or no adverse effects to be used in the treatment. Most of the drugs currently used are composed of heterocyclic structures, as well as many compounds under development that show promising results. In particular a class of compounds, the triazoles, which have wide biological application. Therefore, this study aimed to evaluate heterocyclic compounds derived from triazoles against sensitive strains of Mycobacterium tuberculosis, as candidates for new molecules for the treatment of tuberculosis, through in vitro biological activity studies. The minimum inhibitory concentration index and cytotoxicity in macrophage strain Raw 264.7 and HepG2 hepatocytes of triazole-derived compounds were evaluated, as well as the type of interaction they present with first-line drugs for the treatment of tuberculosis. All compounds showed low to relevant activity against the bacillus, with MIC ranging from 64 to 4 μg/ml for the H37Rv strain and >64 to 8 μg/ml for the H37Ra strain. The compounds with the best results were A48 and A51, selected for evaluation of the activity of the fractioned inhibitory concentration index, with the drugs rifampicin and ethambutol, in which both were indifferent. The results obtained in this study indicate the mycobacterial inhibitory action of the evaluated triazole derivatives, as possible pharmacological agents, offering parameters for the follow-up of in vitro tests.